This phase II trial studies how well clofarabine and melphalan before a donor stem cell transplant works in treating patients with a decrease in or disappearance of signs and symptoms of myelodysplasia or acute leukemia (disease is in remission), or chronic myelomonocytic leukemia. Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into a patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving clofarabine and melphalan before transplant may help prevent the cancer from coming back after transplant, and they may cause fewer side effects than standard treatment.

Progression-free survival [ Time Frame: From start of treatment to the date of death, disease relapse/progression, or last follow-up whichever occurs first, assessed at 2 years ]

Calculated using the Kaplan-Meier product-limit method.

Secondary Outcome Measures:

Overall survival [ Time Frame: From start of treatment until death, or last follow-up, whichever comes first, assessed up to 5 years ]

Calculated using the Kaplan-Meier product-limit method.

Cumulative incidence of relapse/progression [ Time Frame: From start of treatment, assessed up to 5 years ]

Calculated as competing risks using the Gray method.

Cumulative incidence of non-relapse mortality defined as death occurring in a patient from causes other than relapse or progression [ Time Frame: From start of treatment until non-disease death, assessed up to 5 years ]

Calculated as competing risks using the Gray method.

Overall toxicity graded using the Bearman scale and CTCAE v4.03 [ Time Frame: Up to 100 days post-transplant ]

Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

Incidence and severity of acute GVHD of grades 2-4 and 3-4 according to the consensus grading [ Time Frame: Up to 100 days post-transplant ]

The first day of acute GVHD onset at a certain grade will be used to calculate cumulative incidence curves for that GVHD grade.

Incidence and severity of chronic GVHD scored according to National Institute of Health (NIH) consensus staging [ Time Frame: After 100 days post-transplant ]

The first day of chronic GVHD onset will be used to calculate cumulative incidence curves.

Microbiologically documented infection [ Time Frame: Up to 100 days post-transplant ]

Reported by site of disease, date of onset, severity and resolution, if any.

Patients with chronic myelomonocytic leukemia (CMML) are allowed to be enrolled

Patients with MDS that has evolved to AML must be in remission

Patients must not be eligible for full ablative regimens by the attending physician

Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis

Performance status of >= 70% on the Karnofsky scale

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect she is pregnant while participating on the trial, she should inform her treating physician immediately

Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as Flt-3 status) will be obtained as per standard practice

Bone marrow aspirates/biopsies should be performed within 28 (+ 4 day window) days from registration to confirm disease remission status

Diffusing capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) > 45% predicted

Availability of a human leukocyte antigen (HLA) matched (6/6) sibling donor or 8/8 matched unrelated donor; Donors with mismatch at HLA-A, HLA-B, HLA-C, and HLA-DR will be reviewed by matched unrelated donor (MUD) committee and allowed if their mismatch with the recipient does not require additional GVHD prophylaxis (other than tacrolimus and sirolimus), donors with mismatch at HLA-DQ or HLA-DPB are eligible; donor evaluation according to City of Hope (COH) standard operating procedure (SOP)

Donor stem cell source can be either peripheral blood or bone marrow

All patients must have a psychosocial evaluation prior to transplant as per COH SOP

All subjects must have the ability to understand and the willingness to sign a written informed consent

ALL or AML patients who received chemotherapy (induction or consolidation) can proceed to transplant once bone marrow cellularity is > 10 % with no evidence of leukemia

Exclusion Criteria:

Patients who have received a prior autologous or allogeneic transplant are excluded

Patients who have received radiation therapy as part of their leukemia treatment may be ineligible and individual cases must be presented to the study principal investigator (PI) for determination of eligibility

Any psychiatric, social or compliance issues that, in the treating physician's opinion, will interfere with completion of the transplant treatment and follow up

Medical or psychiatric reasons which make the donor unlikely to tolerate or cooperate with filgrastim (G-CSF) therapy or leukapheresis or bone marrow harvest

Known allergies to clofarabine, melphalan, sirolimus or tacrolimus

Patients with other active malignancies (besides AML, ALL, MDS) requiring treatment or where there is concern of progression are ineligible for this study; however, patients with previously treated skin cancer, early stage cervical or prostate cancer may be eligible if there is no evidence of residual disease

Cord blood as a donor source is not acceptable

Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01885689